Fatty Acid Oxidation Defects and Insulin Sensitivity
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Cardiology, Neurology, Endocrine, Metabolic, Metabolic |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology, Neurology, Pharmacology / Toxicology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/19/2018 |
| Start Date: | February 2016 |
| End Date: | April 2020 |
| Contact: | Julie Martin, MS |
| Email: | martijul@ohsu.edu |
| Phone: | 503-494-5313 |
Role of Fatty Acid Oxidation Defects in Insulin Sensitivity
The purpose of this study is to learn more about what causes insulin resistance. It has been
suggested that proper breakdown of fat into energy (oxidation) in the body is important to
allow insulin to keep blood sugar in the normal range. The investigators want to know if
having one of the fatty acid oxidation disorders could have an influence on insulin action.
Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that
converts fat into energy. The investigators will study both normal healthy people and people
with a long-chain fatty acid oxidation disorder.
suggested that proper breakdown of fat into energy (oxidation) in the body is important to
allow insulin to keep blood sugar in the normal range. The investigators want to know if
having one of the fatty acid oxidation disorders could have an influence on insulin action.
Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that
converts fat into energy. The investigators will study both normal healthy people and people
with a long-chain fatty acid oxidation disorder.
The overall goal of this proposal is to investigate the effects of disordered mitochondrial
fatty acid oxidation on insulin resistance in humans. Mitochondrial dysfunction has been
implicated in the development of insulin resistance and type 2 diabetes during excess dietary
fat intake and from increased release of endogenous free fatty acids , such as occurs in
obesity. Controversy exists, however, as to whether this insulin resistance results from
intrinsic defects in mitochondrial energy utilization or from abnormalities resulting from
excess free fatty acid flux, as well as the role that subsequent accumulation of cellular
metabolic intermediates play in impaired insulin signaling.
To address these controversies, the investigators will study a unique population of patients
with inherited defects in each of the three mitochondrial enzymes in the fatty acid oxidation
pathway: 1) very long-chain acyl-CoA dehydrogenase (VLCAD); 2) trifunctional protein (TFP,
which includes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)); and 3) medium-chain
acyl-CoA dehydrogenase (MCAD). These proteins are required for the oxidation of sequentially
shorter fatty acids . The investigators will test the hypothesis that intrinsic defects in
mitochondrial function involving oxidation of long-chain, but not medium-chain, fatty acids
are sufficient to prevent intralipid-induced insulin resistance.
fatty acid oxidation on insulin resistance in humans. Mitochondrial dysfunction has been
implicated in the development of insulin resistance and type 2 diabetes during excess dietary
fat intake and from increased release of endogenous free fatty acids , such as occurs in
obesity. Controversy exists, however, as to whether this insulin resistance results from
intrinsic defects in mitochondrial energy utilization or from abnormalities resulting from
excess free fatty acid flux, as well as the role that subsequent accumulation of cellular
metabolic intermediates play in impaired insulin signaling.
To address these controversies, the investigators will study a unique population of patients
with inherited defects in each of the three mitochondrial enzymes in the fatty acid oxidation
pathway: 1) very long-chain acyl-CoA dehydrogenase (VLCAD); 2) trifunctional protein (TFP,
which includes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)); and 3) medium-chain
acyl-CoA dehydrogenase (MCAD). These proteins are required for the oxidation of sequentially
shorter fatty acids . The investigators will test the hypothesis that intrinsic defects in
mitochondrial function involving oxidation of long-chain, but not medium-chain, fatty acids
are sufficient to prevent intralipid-induced insulin resistance.
Inclusion Criteria:
- confirmed diagnosis of VLCAD, LCHAD, TFP or MCAD deficiency or same gender, age and
BMI as a subject with a fatty acid oxidation disorder
- ability to travel to Oregon Health & Science University, Portland, Oregon
- ability and willingness to complete the protocol
Exclusion Criteria:
- hemoglobin <10g/dl, international normalized ratio (INR) >1.2 Prothrombin time (PTT)
>36 sec, Platelets <150K/mm3
- pregnant or lactating females
- endocrine disorder such as diabetes or untreated thyroid disease
- cardiovascular disease or elevated plasma lipids
- regularly taking meds that strongly affect bleeding, bruising or platelets
We found this trial at
1
site
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Phone: 503-494-5313
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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